HDAC1/HDAC3 modulates PPARG2 transcription through the sumoylated CEBPD in hepatic lipogenesis

Lai, Pei Hua; Wang, Wen Lin; Ko, Chiung Yuan; Lee, Yi Chao; Yang, Wen‐Ming; Shen, Tsung Wei; Chang, Wen Chang; Wang, Ju Ming

doi:10.1016/j.bbamcr.2008.06.008

Cited by 48 publications

(40 citation statements)

References 57 publications

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“…This resulted in a marked increase in liver and serum triglycerides and cholesterol [85]. Further analysis revealed that HDAC1 and HDAC3 but not HDAC2 interacted with sumoylated C/EBP-delta and thereby repressed the transcription of PPAR-gamma 2 which is involved in hepatic lipogenesis [86,87]. These results point to a critical role for HDAC3 in liver lipid metabolism.…”

Section: Histon Deacetylases (Hdacs)mentioning

confidence: 83%

Transcriptional co-factors and hepatic energy metabolism

Sommerfeld

Krones-Herzig

Herzig

2011

Molecular and Cellular Endocrinology

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After binding to their cognate DNA-binding partner, transcriptional co-factors exert their function through the recruitment of enzymatic, chromatin-modifying activities. In turn, the assembly of co-factor-associated multi-protein complexes efficiently impacts target gene expression. Recent advances have established transcriptional co-factor complexes as a critical regulatory level in energy homeostasis and aberrant co-factor activity has been linked to the pathogenesis of severe metabolic disorders including obesity, type 2 diabetes and other components of the Metabolic Syndrome. The liver represents the key peripheral organ for the maintenance of systemic energy homeostasis, and aberrations in hepatic glucose and lipid metabolism have been causally linked to the manifestation of disorders associated with the Metabolic Syndrome. Therefore, this review focuses on the role of distinct classes of transcriptional co-factors in hepatic glucose and lipid homeostasis, emphasizing pathwayspecific functions of these co-factors under physiological and pathophysiological conditions.

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Section: Histon Deacetylases (Hdacs)mentioning

confidence: 83%

Transcriptional co-factors and hepatic energy metabolism

Sommerfeld

Krones-Herzig

Herzig

2011

Molecular and Cellular Endocrinology

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“…Cross-linking was reversed and immunoprecipitated chromatin was amplified with primers corresponding to specific regions in the PPARG2 or GADD153 genomic loci. The ChIP primers for the PPARG2 promoter have been described (20). The ChIP primers for the GADD153 promoter are as follows:…”

Section: Chromatin Immunoprecipitation Assaysmentioning

confidence: 99%

“…Chromatin immunoprecipitation (ChIP) assays were performed as described (16,20). Briefly, A431 cells were treated with 1% formaldehyde for 15 minutes.…”

Section: Chromatin Immunoprecipitation Assaysmentioning

confidence: 99%

CEBPD Reverses RB/E2F1-Mediated Gene Repression and Participates in HMDB-Induced Apoptosis of Cancer Cells

Pan

et al. 2010

Clinical Cancer Research

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Purpose: Recent evidence indicates that a tumor suppressor gene CEBPD (CCAAT/enhancer-binding protein delta) is downregulated in many cancers including cervical cancer, which provides a therapeutic potential associated with its reactivation. However, little is known for CEBPD activators and the effect of reactivation of CEBPD transcription upon anticancer drug treatment. In this study, we identified a novel CEBPD activator, 1-(2-hydroxy-5-methylphenyl)-3-phenyl-1,3-propanedione (HMDB). The purpose of this study is to characterize the mechanism of HMDB-induced CEBPD activation and its potential effect in cancer therapy.Experimental Design: Methylation-specific PCR assay, reporter assay, and chromatin immunoprecipitation (ChIP) assay were performed to dissect the signaling pathway of HMDB-induced CEBPD transcription. Furthermore, a consequence of HMDB-induced CEBPD expression was linked with E2F1 and retinoblastoma (RB), which discloses the scenario of CEBPD, E2F1, and RB bindings and transcriptional regulation on the promoters of proapoptotic genes, PPARG2 and GADD153. Finally, the anticancer effect of HMDB was examined in xenograft mice.Results: We demonstrate that CEBPD plays an essential role in HMDB-mediated apoptosis of cancer cells. HMDB up-regulates CEBPD transcription through the p38/CREB pathway, thus leading to transcriptional activation of PPARG2 and GADD153. Furthermore, increased level of CEBPD attenuates E2F1-induced cancer cell proliferation and partially rescues RB/E2F1-mediated repression of PPARG2 and GADD153 transcription. Moreover, HMDB treatment attenuates the growth of A431 xenografts in severe combined immunodeficient mice mice.Conclusions: These results clearly demonstrate that HMDB kills cancer cells through activation of CEBPD pathways and suggest that HMDB can serve as a superior chemotherapeutic agent with limited potential for adverse side effects. Clin Cancer Res; 16(23); 5770-80. Ó2010 AACR.

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“…The p38 MAPK/cAMP response element-binding protein (CREB) pathway contributes to HMDB-induced CEBPD activation (12). Increased CEBPD participates in the transcription of peroxisome proliferator-activated nuclear receptor g 2 (PPARG2), an adipogenic and proapoptotic inducer, and DNA-damage-inducible protein 153 (GADD153, also known as CHOP), a proapoptotic inducer (13,14). A recent study demonstrated that loss of CEBPD might contribute to the initiation of breast cancer (15).…”

Section: Introductionmentioning

confidence: 99%

HMDB and 5-AzadC Combination Reverses Tumor Suppressor CCAAT/Enhancer-Binding Protein Delta to Strengthen the Death of Liver Cancer Cells

Tsai

et al. 2015

Molecular Cancer Therapeutics

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Hepatocellular carcinoma (HCC) can arise from chronic inflammation due to viral infection, organ damage, drug toxicity, or alcohol abuse. Moreover, gene desensitization via aberrant CpG island methylation is a frequent epigenetic defect in HCC. However, the details of how inflammation is linked with epigenetic-mediated desensitization of tumor suppressor genes remains less investigated. In this study, we found that loss of CEBPD enhances the growth of liver cancer cells and is associated with the occurrence of liver cancers, as determined by the assessment of clinical specimens and in vivo animal models. Moreover, E2F1-regulated epigenetic axis attenuated CEBPD expression in liver cancer cells. CEBPD is responsive to the hydroxymethyldibenzoylmethane (HMDB)-induced p38/ CREB pathway and plays an important role in the HMDBinduced apoptosis of cancer cells. Regarding depression of epigenetic effects to enhance HMDB-induced CEBPD expression, the combination of HMDB and 5-Aza-2 0 -deoxycytidine (5-AzadC) could enhance the death of liver cancer cells and reduce the tumor formation of Huh7 xenograft mice. In conclusion, these results suggest that CEBPD could be a useful diagnostic marker and therapeutic target in HCC. The results also reveal the therapeutic potential for low-dose 5-AzadC to enhance the HMDB-induced death of HCC cells.

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HDAC1/HDAC3 modulates PPARG2 transcription through the sumoylated CEBPD in hepatic lipogenesis

Cited by 48 publications

References 57 publications

Transcriptional co-factors and hepatic energy metabolism

Transcriptional co-factors and hepatic energy metabolism

CEBPD Reverses RB/E2F1-Mediated Gene Repression and Participates in HMDB-Induced Apoptosis of Cancer Cells

HMDB and 5-AzadC Combination Reverses Tumor Suppressor CCAAT/Enhancer-Binding Protein Delta to Strengthen the Death of Liver Cancer Cells

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